Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study

Abstract

Plasma lipoprotein alterations in nine insulin-dependent diabetics with hyperlipemia have been related to the lipid accumulating in eruptive xanthomas evolving in these patients. Histochemical and electron microscopic examination of xanthomas have been correlated with the lipid analyses in order to obtain additional evidence regarding the lipoprotein origin of lipids accumulating in the lesions. Both analytical and morphologic evidence suggested that circulating chylomicrons significantly contribute to the xanthoma lipids. All the patients had large quantities of circulating triglyceriderich chylomicrons which carried approximately 70% of the triglyceride found in the plasma. The fatty acid pattern of chylomicron and xanthoma triglycerides were similar. Triglyceride constituted the major lipid found in the xanthomas when they were sampled during their eruption. These findings, take in conjunction with histochemical and electron microscopic evidence of chylomicron particles in the dermal capillary walls, support the theory that blood lipoproteins, and particularly chylomicrons, permeated the vascular walls and the triglycerides carried by these lipoproteins apparently accumulated in tissue macrophages and perithelial cells which evolved into foam cells. Initiation of appropriate therapy resulted in clearance of the chylomicronemia and a concomitant resolution of the xanthomas as reflected by a decrease in total xanthoma lipid. Sequential studies of resolving xanthomas in five patients revealed that xanthoma triglyceride was mobilized more rapidly than cholesterol, resulting in a redistribution of the xanthoma lipids, so that the resolving lesions were cholesterol rich. Consistent with this change in lipid composition, correlative electron microscopy revealed loss of amorphous material from many of the foam cell vacuoles.